Correspondence Address:Kapildev DasDepartment of Dermatology, School of Tropical Medicine, Kolkata, West Bengal India

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DOI: 10.4103/0253-7613.106444

PMID: 23543097

» Abstract

Pseudotumor cerebri (PTC) is a rare neurological disorder characterized by increased intracranial pressure in absence of any intra-cranial space-occupying lesion. It is mostly due to impairment of drainage of CSF from arachnoid villi. Clinically pseudotumor cerebri presents with headache, diplopia, nausea, vomiting, papilloedema and if treatment is delayed, may lead to blindness. Females of childbearing age group, endocrinal abnormalities and ingestion of certain drugs have been reported to be associated with pseudotumor cerebri. However, it's occurrence in relation to acitretin ingestion has not been reported on pubmed database. Here we present a case where significant temporal association of acitretin intake with PTC was found in a child who was being treated with this medication for recalcitrant pustular psoriasis. The case is reported for its rarity in occurrence and associated significant morbidity including visual loss if not diagnosed and treated immediately. According to Naranjo ADR Causality scale of adverse drug reaction, the association of PTC due to acitretin in our case was probable.

Pseudotumor cerebri (PTC), is a neurological disorder that is characterized by increased intracranial pressure in the absence of a tumor or other diseases. It affects predominantly obese women of childbearing age with male to female ratio of 1: 8. [1],[2] However, childhood cases are not rare and till date about 770 cases of childhood PTC have been reported. PTC is a disorder of unknown etiology. Present hypothesis is resistance to cerebrospinal fluid (CSF) outflow at the arachnoid granulations that line the dural venous sinuses through which CSF reabsorption occurs, is responsible for PTC. The common risk factors for development of PTC include female sex of reproductive age group, obesity, recent weight gain, menstrual irregularity. [3] Several medications have been reported to cause PTC including cimetidine, corticosteroids, danazol, isotretinoin, levothyroxine, lithium, minocycline, nalidixic acid, nitrofurantoin, tamoxifen, tetracyclines, trimethoprim-sulfamethoxazole, levonorgestrel implant, recombinant human growth hormone, vitamin A etc. [4],[5],[6],[7],[8],[9],[10],[11]

However, there is no case report of PTC due to acitretin found through pubmed Search. Here we report a case where a child with recalcitrant pustular psoriasis developed PTC showing significant temporal association of occurrence of PTC with intake of acitretin.

» Case Report

A 12-years-old boy with generalized pustular psoriasis attended the outpatient department of a tertiary care hospital of eastern India. Initially he was treated with methotrexate for two months in the local hospital with inadequate response and was referred to us. When he attended to us, more than 70% of the body surface area showed tenderness, erythema and were studded with pustules. After baseline investigations we put the patient on 25 mg of acitretin per day. After 10 days the dosage was increased to 35 mg/day. After one month of acitretin therapy the pustular lesions were gone and significant improvement in erythema and scaling was noticed.

After one and half month, the patient complained of nausea, headache and vomiting. Antiemetic medicines were used with no result. Three days later patient complained of blurring of vision, diplopia and lacrimation. A diagnosis of PTC was suspected and the patient was sent for ophthalmological checkup, which revealed papilledema. There was no fever, neck rigidity, neurological deficit.

Based on history, clinical features, and laboratory findings diagnosis of PTC was made. Patient was referred to consultant neurologist. Acitretin was stopped. He was put on intravenous mannitol, oral acetazolamide and systemic corticosteroid. The symptoms like nausea, diplopia, and headache waned within three days. Repeat ophthalmological examination after three days revealed disappearance of papilledema. Gradually, the dose of systemic steroid was tapered off and the patient was put on cyclosporine. With cyclosporine dose 2.5mg/kg, psoriasis was adequately controlled within two weeks.

» Discussion

Acitretin, a second generation synthetic retinoid, has several dermatological indications including psoriasis, congenital ichthyoses and keratoderma, Palmoplantar pustulosis, Darier disease, Pityriasis rubra pilaris, Lichen planus, Lichen sclerosus, hyperkeratotic hand eczema and Prevention of malignancy. [12] Though in case of chronic plaque psoriasis acitretin is effective but it is mostly implicated in the treatment of generalized pustular psoriasis. A study by Ozawa A. et al described that the responsiveness of pustular psoriasis to methotrexate was 76%, for cyclosporine it was 71% while the responsiveness was 84% for acitretin. [13] The limiting factor for the use of Acitretin is its side effects. Those include teratogenicity, dry eye, reduced night vision, premature epiphyseal closure, dyslipidemia, pancreatitis, leucopenia, agrnaulocytosis, hepatic and renal impairment, myopathy, pseudotumour cerebri etc.

Pseudotumor cerebri is a neurological disorder that is characterized by increased intracranial pressure in absence of any space occupying lesion. It is mostly due to impairment of CSF from aracnoid villi. Risk factors for the development of PTC include female with child bearing age group, endocrinal disturbances and ingestion of certain medications including Cimetidine, corticosteroids, danazol, isotretinoin, levothyroxine, lithium, minocycline, nalidixic acid, nitrofurantoin, tamoxifen, tetracycline, trimethoprim-sulfamethoxazole, levonorgestrel implant, Recombinant human growth hormone, Vitamin A etc. [4],[5],[6],[7],[8],[9],[10],[11]

Although Isotretinion have been commonly reported to cause pseudotumor cerebri in young adult women treated for acne, there is paucity of data regarding occurrence of PTC in relation to acitretin.

Here we present the case where significant temporal association of acitretin with PTC was found in a child who was treated with this medication for recalcitrant pustular psoriasis. The reaction appeared after the drug was introduced. There was no previous history of similar drug intake in the past. Significant clinical improvement was noted when the drug was discontinued. Considering the seriousness of the condition, we did not reintroduced acitretin in this patient. With through history taking, clinical examination and available laboratory investigations we could not found any other etiology for this constellation of symptoms. After the discontinuation of the drug, considering severity of pustular psoriasis, cyclosporine was introduced. Within few days his clinical condition had improved without any further aggravation of PTC. Due to lack of logistic support, detection of the drug concentration in the body fluid could not be carried out. After the diagnosis of PTC, acitretin was abruptly discontinued. With thorough pubmed search we could not find any case report regarding occurrence of PTC due to acitretin. As par Naranjo Causality scale of adverse drug reaction, the score was five. [14] Hence, according to Naranjo Casualty assessment scale the association of PTC due to acitretin in our case is probable. The case is reported for its rarity in occurrence and associated significant morbidity including visual loss if not diagnosed and treated immediately.